PROJECT SUMMARY Pediatric-onset hemiplegia (PH) causes movement impairments on one side of the body and accounts for more than a third of all cases of cerebral palsy, the most common motor disability in childhood. Motor impairments in this population include weakness, movement synergies, and coupling movements between limbs (between arms and between paretic arm and legs), all of which limit independence with functional mobility throughout the lifespan. Crucial tasks, such as reaching and grasping, required for countless daily activities including participating in the classroom, become limited or impossible. In the previous cycle of this R01, we discovered that the timing of brain injury during neurodevelopment impacted the expression of weakness, involuntary coupling of shoulder abduction with elbow, wrist, and finger flexion (flexion synergy), and involuntary coupling between upper limbs during isometric tasks. Our previous work uncovered the importance of the timing of the injury on the preservation of neural structures, expressed in the integrity of white matter, as they may be affected differently based on the stage of neurodevelopment when the injury occurs. During early injuries (PRE-natal), there may be preservation of direct ipsilateral corticospinal projections that are present as part of typical neural development. We hypothesize that this explains the reduced presence of the flexion synergy and the greater movement coupling between upper limbs. Conversely, in later injuries (PERI- and POST-natal) we hypothesize that the developmental pruning of these ipsilateral corticospinal projections is in process (PERI-natal) or has already occurred (POST-natal) leading to increased reliance in indirect ipsilateral corticoreticulospinal pathways to control movement of the paretic limbs. These indirect pathways branch significantly at the spinal cord, explaining the presence of the flexion synergy and abnormal involuntary coupling between the paretic leg and arm. In an effort to determine the effects of time of injury and limb loading on motor impairments during functional reaching-grasping tasks in PH and the link to neural microstructural morphology, we propose to: 1) quantify upper extremity reaching distance and hand opening/closing ability; 2) determine the expression of between-limb movement coupling; and 3) identify the changes in white and gray matter complexity of motor pathways in ipsilesional and contralesional hemispheres as well as the brainstem. As such, the proposed research will, for the first time, investigate the effect of time of brain injury on motor pathway complexity in individuals with pediatric-onset hemiplegic who express within-limb and between-limb coupling dysfunction. This will provide the foundation for the development of more effective targeted, time-of-injury specific interventions for the treatment of abnormal within- and between-limb coupling to improve functional capabilities in this population.